ER stress induced immunopathology involving complement in CADASIL: implications for therapeutics.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by NOTCH3 mutations. Typical CADASIL is characterised by subcortical ischemic strokes due to severe arteriopathy and fibrotic thickening of small arteries. Arteriolar vascular smooth muscle cells (VSMCs) are the key target in CADASIL, but the potential mechanisms involved in their degeneration are still unclear. Focusing on cerebral microvessels in the frontal and anterior temporal lobes and the basal ganglia, we used advanced proteomic and immunohistochemical methods to explore the extent of inflammatory and immune responses in CADASIL subjects compared to similar age normal and other disease controls. There was variable loss of VSMC in medial layers of arteries in white matter as well as the cortex, that could not be distinguished whether NOTCH3 mutations were in the epidermal growth factor (EGFr) domains 1-6 or EGFr7-34. Proteomics of isolated cerebral microvessels showed alterations in several proteins, many associated with endoplasmic reticulum (ER) stress including heat shock proteins. Cerebral vessels with sparsely populated VSMCs also attracted robust accrual of perivascular microglia/macrophages in order CD45+ > CD163+ > CD68+cells, with > 60% of vessel walls exhibiting intercellular adhesion molecule-1 (ICAM-1) immunoreactivity. Functional VSMC cultures bearing the NOTCH3 Arg133Cys mutation showed increased gene expression of the pro-inflammatory cytokine interleukin 6 and ICAM-1 by 16- and 50-fold, respectively. We further found evidence for activation of the alternative pathway of complement. Immunolocalisation of complement Factor B, C3d and C5-9 terminal complex but not C1q was apparent in ~ 70% of cerebral vessels. Increased complement expression was corroborated in > 70% of cultured VSMCs bearing the Arg133Cys mutation independent of N3ECD immunoreactivity. Our observations suggest that ER stress and other cellular features associated with arteriolar VSMC damage instigate robust localized inflammatory and immune responses in CADASIL. Our study has important implications for immunomodulation approaches to counter the characteristic arteriopathy of CADASIL.

Translating economic evaluations into financing strategies for implementing evidence-based practices.

BACKGROUND: Implementation researchers are increasingly using economic evaluation to explore the benefits produced by implementing evidence-based practices (EBPs) in healthcare settings. However, the findings of typical economic evaluations (e.g., based on clinical trials) are rarely sufficient to inform decisions about how health service organizations and policymakers should finance investments in EBPs. This paper describes how economic evaluations can be translated into policy and practice through complementary research on financing strategies that support EBP implementation and sustainment. MAIN BODY: We provide an overview of EBP implementation financing, which outlines key financing and health service delivery system stakeholders and their points of decision-making. We then illustrate how economic evaluations have informed decisions about EBP implementation and sustainment with three case examples: (1) use of Pay-for-Success financing to implement multisystemic therapy in underserved areas of Colorado, USA, based in part on the strength of evidence from economic evaluations; (2) an alternative payment model to sustain evidence-based oncology care, developed by the US Centers for Medicare and Medicaid Services through simulations of economic impact; and (3) use of a recently developed fiscal mapping process to collaboratively match financing strategies and needs during a pragmatic clinical trial for a newly adapted family support intervention for opioid use disorder. CONCLUSIONS: EBP financing strategies can help overcome cost-related barriers to implementing and sustaining EBPs by translating economic evaluation results into policy and practice. We present a research agenda to advance understanding of financing strategies in five key areas raised by our case examples: (1) maximize the relevance of economic evaluations for real-world EBP implementation; (2) study ongoing changes in financing systems as part of economic evaluations; (3) identify the conditions under which a given financing strategy is most beneficial; (4) explore the use and impacts of financing strategies across pre-implementation, active implementation, and sustainment phases; and (5) advance research efforts through strong partnerships with stakeholder groups while attending to issues of power imbalance and transparency. Attention to these research areas will develop a robust body of scholarship around EBP financing strategies and, ultimately, enable greater public health impacts of EBPs.

Internet-Based Patient Survey on Urolithiasis Treatment and Patient Satisfaction.

PURPOSE: We created an Internet-based survey of patients treated for urolithiasis to evaluate for trends in treatment, outcome, and patient satisfaction and to establish internet surveys as a feasible medium for future research of patient urolithiasis treatment experiences. MATERIALS AND METHODS: We used the website "kidneystoners.org" to disseminate the online survey, which queried respondents on treatment type, outcome, and satisfaction. Patient satisfaction was correlated with treatment type and outcome. Chi-square and analysis of variance tests were used to compare responses between treatment types. RESULTS: Four hundred forty-three respondents completed the survey. The majority (46%) were treated ureteroscopically, followed by extracorporeal shock wave lithotripsy (SWL, 25%) and percutaneous nephrolithotomy (7%). Other treatments included spontaneous passage (13%), medical expulsive therapy (7%), and home remedies (2%). Sixty-four percent of respondents deemed their treatment "successful," while 36% reported their treatment as either "partially successful" or "unsuccessful." Unsuccessful treatment was more likely for SWL (17%) and home remedies (14%) (p=0.002). Most respondents (52%) reported being either satisfied or very satisfied with their treatment choice. Satisfaction did not vary significantly by treatment type, but was significantly associated with treatment success (mean satisfaction 3.8/5 for "successful" vs 1.9/5 for "unsuccessful" treatment; p<0.0001). CONCLUSION: Use of the Internet allows rapid gathering of patient information from a large geographic distribution. Our survey is consistent with previous studies in demonstrating an increased use of ureteroscopy to treat both renal and ureteral calculi. In general, patients are satisfied with treatment outcomes despite a large percentage of people reporting needing to have secondary procedures.

Patient experiences and preferences with ureteral stent removal.

PURPOSE: Ureteral stent removal is a source of patient morbidity. We surveyed 599 patients to evaluate their experiences and identify the preferred method of stent removal. MATERIALS AND METHODS: Visitors to a kidney stone website were invited to participate. Respondents were asked how their ureteral stent was removed? Pain during and after the procedure, patient experiences, and preferences regarding stent removal were queried. Chi-square and ANOVA tests were used to identify significant differences among removal methods. RESULTS: Five hundred seventy-one respondents were included in the study. The majority of stents (44%) were removed by office cystoscopy while 39% had their stents removed by string. Mean pain during stent removal was 4.8 out of 10 with 57% reporting moderate-to-severe pain levels of 4 or more. Removal by office cystoscopy resulted in the highest experienced pain (5.3). Thirty-two percent reported delayed severe pain after stent removal, including 9% who returned for emergency care. Removal by string resulted in more emergency room visits when compared to cystoscopy. Willingness to undergo the same removal technique was lowest for those who underwent office cystoscopy and highest for operating room cystoscopy. Being informed of why a stent was placed and the removal process was of high priority for respondents. CONCLUSIONS: The majority of patients report moderate-to-severe pain with stent removal and a third report delayed significant pain after stent removal. Variations exist in the patient experience with stent removal based on the method used. More research is needed to identify effective ways to prevent or manage stent-removal-related adverse events.

Brain microvascular accumulation and distribution of the NOTCH3 ectodomain and granular osmiophilic material in CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of familial brain arteriopathy, is associated with deposition of granular osmiophilic material (GOM). We used immunohistochemistry and immunogold electron microscopy (EM) to examine the distribution of GOM and NOTCH3 ectodomain (N3ECD) protein in microvasculature of brain gray matter and white matter in patients with CADASIL, non-CADASIL hereditary small-vessel disease and sporadic age-related degenerative disease, and comparable-age controls. We observed intense immunostaining patterns with 2 different anti-N3ECD antibodies in CADASIL but not in young and older controls or other small-vessel disease patients. In addition, CADASIL samples exhibited immunoreactivity in arterial walls and in most capillaries. Electron microscopy revealed profound and widespread extracellular distribution of 0.2- to 2-µm GOM deposits associated with meningeal vessels and perforating arteries and arterioles. Granular osmiophilic material was adjacent to capillaries even within white matter. Immunogold EM with antibody A1-1 to N3ECD revealed abundant particles in GOM within microvessels, vascular smooth muscle cell membranes, and perivascular cells. Granular osmiophilic material did not exhibit immunogold labeling for smooth muscle α-actin or collagen IV. These results showed the specificity of the antibodies and confirm the predominant localization of N3ECD within GOM deposits. The extensive distribution of N3ECD-GOM complexes within meninges, arteries, arterioles, and particularly capillaries in the brains of CADASIL patients suggests that NOTCH3 fragments are major components of GOM deposits, which may be eliminated via perivascular routes.

Urolithiasis risk factors in the bariatric population undergoing gastric bypass surgery.

BACKGROUND: Previous studies have suggested an increased risk of forming symptomatic urolithiasis after Roux-en-Y gastric bypass (RYGB) attributed to the development of hyperoxaluria. The objective of our investigation was to evaluate changes in the urine milieu after RYGB that might explain the increased risk of urolithiasis. METHODS: Patients underwent serum and urine chemistry tests 1 week before and 6 months after RYGB at a university hospital. The postoperative urolithiasis risk factors were compared with the preoperative values. Statistical analysis was performed using paired t tests. Significant changes were identified as P ≤ .05. RESULTS: A total of 38 patients (7 men and 31 women) submitted samples both before and after RYGB. The mean patient weight had decreased from 131 kg to 92 kg. The mean serum creatinine decreased from .83 to .72 mg/dL (P = .0004). Urinary changes known to increase the risk of urolithiasis include a decrease in volume (2-1.5 L/d, P = .03), an increase in calcium (139-182 mg/d, P = .04), and an increase in oxalate (38-48 mg/d, P < .001). The urinary supersaturation indexes for calcium oxalate (4.9-10.5, P < .001) increased. CONCLUSION: Our results confirm that patients undergoing RYGB develop changes in the urinary milieu predisposing them to forming urinary stones. Urolithiasis risk is multifactorial and is related to more than just hyperoxaluria. A patient's long-term risk of developing stones and the effect on renal function is unknown. Preoperative counseling of patients regarding their risk of forming stones and dietary counseling to minimize their risk of developing stones postoperatively is warranted.

Changes in renal function following Roux-en-Y gastric bypass: a prospective study.

BACKGROUND: Studies of the impact of Roux-en-Y gastric bypass (RYGB) on renal function have shown mixed results. We constructed this prospective repeated-measures controlled study to characterize this response and identify the best method of gauging renal function in this setting. METHODS: Clinical data, serum creatinine (SC), and 24-h urine were collected 1 week before and 6 months following RYGB. Glomerular filtration rate (GFR) was calculated utilizing the Modification of Diet in Renal Disease formula. Creatinine clearance (CCL) was measured as a 24-h collection (24 CCL) and calculated by the Cockcroft-Gault (CG) formula. RESULTS: The study population of 37 patients (81% women) had a mean age of 47 ± 11 years, had mean BMI of 47.6 ± 6.3 kg/m(2), and achieved a mean % excess weight loss (EWL) of 60.9 ± 17.1%. SC decreased from 0.83 ± 0.21 mg/dl to 0.72 ± 0.16 mg/dl (p < 0.001) and mean GFR improved from 91.6 ± 29.7 ml/min/1.73 m(2) to 104.9 ± 23.5 ml/min/1.73 m(2) (p < 0.01). Preoperatively, CG significantly overestimated CCL when compared with 24 CCL (197.1 ± 88.2 ml/min vs. 136.5 ± 53.0 ml/min, p < 0.001). In all patients, improvement in 24 CCL correlated with EWL (r = 0.32) and %EWL (r = 0.16), and significantly correlated with decrease in BMI (r = 0.51, p < 0.005). In hypertensive patients, improvement in 24 CCL significantly correlated with EWL (r = 0.43, p < 0.05), %EWL (r = 0.40, p < 0.05), and decrease in BMI (r = 0.60, p < 0.001) and was negatively correlated with age (r = -0.45, p < 0.05). CONCLUSIONS: This study demonstrates that renal function improves following RYGB and is best identified by change in GFR. Improvement in 24 CCL is correlated with the EWL success of the patient, especially hypertensive patients.

RNAase-III enzyme Dicer maintains signaling pathways for differentiation and survival in mouse cortical neural stem cells.

An important function of the RNAase-III enzyme Dicer is to process microRNA precursors into ~22-nucleotide non-coding small RNAs. But little is known about the role of Dicer in mammalian brain formation and neural stem cell (NSC) development. Here we show that Dicer plays a crucial role in controlling mouse cortical NSC development. We found that Dicer function is essential for expanding cortical neural progenitors and NSCs. We have identified a population of Dicer-deficient NSCs that can self-renew, and that display normal karyotype and heterochromatin protein expression levels but show enlarged nuclei. Dicer-deficient NSCs display abnormal differentiation and undergo cell death when mitogens are withdrawn. Dicer deletion affects the levels of many proteins, as revealed by a mass spectrometry proteomic approach. We have found that an increase of anti-survival and/or pro-apoptosis proteins and a decrease of pro-survival and/or anti-apoptosis proteins contribute to the cell death of Dicer-deficient NSCs, implying a general role for Dicer in protecting cells from apoptosis. Our results demonstrate important functions for Dicer in regulating NSC development by maintaining proper signaling pathways related to cell survival and differentiation.

Rapid onset renal deterioration in an adult with silent ureteropelvic junction obstruction.

We report a case of a rapid renal deterioration due to ureteropelvic junction obstruction (UPJO) in an asymptomatic woman with prior normal diuretic renography. This case illustrates "silent" renal obstruction and the inability of diuretic renography in detecting significant renal obstruction. This case may favor close surveillance of any adult patient with potential UPJO, especially those with underlying renal disease or solitary kidney.

Neuropathological correlates of temporal pole white matter hyperintensities in CADASIL.

BACKGROUND AND PURPOSE: White matter (WM) hyperintensities on MRI or leukoaraiosis is characteristic of stroke syndromes. Increased MRI signals in the anterior temporal pole are suggested to be diagnostic for cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), with 90% sensitivity and 100% specificity. The structural correlates of these specific WM hyperintensities seen on T2-weighted and FLAIR sequences in the temporal pole of CADASIL are unclear. We assessed pathological changes in postmortem tissue from the temporal pole to reveal the cause of CADASIL-specific WM hyperintensities. METHODS: A combination of tinctorial and immunostaining approaches and in vitro imaging methods were used to quantify the extent of perivascular space (PVS), arteriosclerosis determined as the sclerotic index, WM myelination as the myelin index, and damage within the WM as accumulated degraded myelin basic protein in samples of the anterior temporal pole from 9 CADASIL and 8 sporadic subcortical ischemic vascular dementia cases, and 5 similarly aged (young) and 5 older controls. Luxol fast blue-stained serial sections from a CADASIL case were also used to reconstruct the temporal pole, which was then compared to the MR images. RESULTS: Luxol fast blue sections used to reconstruct the temporal pole revealed an abundance of enlarged PVS in the WM that topographically appeared as indistinct opaque regions. The mean and total areas of the PVS per WM area (%PVS) were significantly greater in CADASIL compared to the controls. The myelin index was severely reduced in CADASIL in relation to the subcortical ischemic vascular dementia and control sample that was consistent with increased immunoreactivity of degraded myelin basic protein, indicating myelin degeneration. Cerebral microvessels associated with the PVS exhibited a 4.5-fold greater number of basophilic (hyalinized) vessels and a 57% increase in the sclerotic index values in CADASIL subjects compared to young controls. A significant correlation between the quantity of hyalinized vessels and sclerotic index values was also apparent (P<0.05). CONCLUSIONS: Our findings suggest that MRI hyperintensities in the temporal pole of CADASIL patients are explained by enlarged PVS and degeneration of myelin accompanied by lack of drainage of the interstitial fluid rather than lacunar infarcts. Consistent with the lack of MR hypersignals in the temporal pole of older subcortical ischemic vascular dementia subjects, our observations imply greater progression of pathological changes in CADASIL patients.

MR determination of glomerular filtration rate in subjects with solitary kidneys in comparison to clinical standards of renal function: feasibility and preliminary report.

This study was conducted to demonstrate the feasibility of quantifying single kidney glomerular filtration rate (skGFR) by magnetic resonance (MR) by comparison to the clinical estimates of GFR in volunteer subjects with a single kidney. Seven IRB-approved subjects with a solitary kidney, stable serum creatinine (SCr) and a 24 h creatinine clearance (CrCl) volunteered to undergo an MR examination that determined renal extraction fraction (EF) with a breathhold inversion recovery echo planar pulse sequence and renal blood flow with a velocity encoded phase imaging sequence. The product of EF and blood flow determines GFR. These values were compared with the 24 h CrCl, estimated GFR by the modification of diet in renal disease (MDRD) regression analysis and the Cockroft-Gault (CG) determination of CrCl. The mean and standard deviation of differences between the MR GFR, MDRD and CG vs the 24 h CrCl were 12.3+/-35.7, -8.9+/-18.5 and 1.2+/-19.6, respectively. The Student t-test showed that none of the mean differences were statistically significant between techniques. This clinical investigation shows that MR can be used for skGFR determination in human subjects with comparable values to those derived from clinically used serum-based GFR estimation techniques.

Use of a surgical helmet system to minimize splash injury during percutaneous renal surgery in high-risk patients.

The transmission risk to surgeons performing percutaneous renal surgery on patients who are infected with human immunodeficiency virus/acquired immunodeficiency syndrome, hepatitis B, or hepatitis C is unknown. A recent study found 55% of surgeons' masks contain evidence of blood splash contamination after percutaneous nephrolithotomy. While the risk of infectious disease transmission to the surgeon after mucocutaneous exposure is unknown, the incapacitating disease these pathogens cause can have a devastating and permanent effect on a surgeon's career. We describe our use of a surgical helmet system when performing percutaneous renal surgery on high-risk patients to minimize risk of splash injury and transmission of blood-borne pathogens.

Identification and molecular characterization of a novel PDE4D11 cAMP-specific phosphodiesterase isoform.

Here we report the cloning and characterization of a novel PDE4D isoform (PDE4D11) identified in mouse brain cDNA. This novel isoform has a unique isoform-specific 5'-UTR and N-terminal sequence, whereas, downstream regulatory N-terminal and catalytic C-terminal regions are homologous to other long PDE4D isoforms (Ex2-15). In silico analysis of PDE4D11 cDNA transcript identified the predicted translational start site and the use of a different transcriptional start site compared to other PDE4D isoforms. This isoform is ubiquitously expressed in different mouse tissues, particularly in the brain, liver and spleen. In the brain, PDE4D11 expression levels increased in the cerebellum, but decreased in the hippocampus with progressive age, highlighting a potential role for this isoform in the development of the brain. When transfected in vitro into murine neuroblastoma cells PDE4D11_EGFP expression is cytosolic, consistent with other long PDE4D isoforms. The appearance of cytosolic protein aggregates in discrete microdomains with this isoform, however, may represent a method of compartmentalizing PDE4D11 activity. The novel 5'-sequence of PDE4D11 is conserved among higher vertebrates including human, monkey, dog, horse and rat. Identification of this new isoform highlights the mutliplicity of unique PDE4D isoforms and their potential importance in regulating cAMP levels through compartmentalization and cell-specific expression and underscores the importance of understanding the functional role of each isoform in the development of specific drugs for the treatment of memory disorders.

Evaluation of the impact and need for use of a safety guidewire during ureteroscopy.

BACKGROUND AND PURPOSE: The routine use of a "safety" guidewire adjacent to the ureteroscope during upper tract endoscopy is advocated in surgical texts and by many endourologists. Our experience has led us to theorize that a safety guidewire complicates ureteroscopy by providing resistance to introduction of the endoscope and by creating an obstruction to ureteroscopic instrumentation. To examine our theory, we developed a porcine animal model to evaluate the impact of the presence of a safety guidewire and reviewed our clinical experience, which routinely does not use a safety guidewire during ureteroscopy. PATIENTS AND METHODS: An ex vivo model was created using the excised urinary tract of freshly slaughtered pigs. The forces needed to advance both a semirigid and flexible ureteroscope in the ureter were measured with and without the presence of a 0.035-inch safety guidewire. The clinical records of all patients undergoing ureteroscopy over a 4-year period were reviewed. RESULTS: On average, an additional 12 and 20 g of force were needed to introduce the semirigid and flexible ureteroscope when a guidewire was present. For the chosen study period, 361 patients underwent ureteroscopic procedures without the placement of a safety guidewire. No patient experienced an intraoperative complication related to the absence of a safety wire. CONCLUSIONS: The presence of a safety guidewire adjacent to the endoscope inhibits passage of the ureteroscope in an in vitro animal model. Technologic advancements in ureteroscope design and use of the holmium laser lithotrite minimize ureteral trauma and obviate the need for routine use of a safety wire during ureteroscopy.

Current laparoscopy training in urology: a comparison of fellowships governed by the Society of Urologic Oncology and the Endourological Society.

BACKGROUND AND PURPOSE: Laparoscopic surgery is now an integral technique in the practice of urology, particularly in the management of certain urologic malignancies. Advanced laparoscopy training in urology is primarily reserved for those pursuing fellowship training and is offered both by traditional endourology fellowships and increasingly in urologic oncology fellowships. The purpose of our study was to evaluate and compare current laparoscopy training at the fellowship level. MATERIALS AND METHODS: A 17-item questionnaire was developed with support from both the Endourological Society (EUS) and Society of Urologic Oncology (SUO). Surveys were sent to program directors of fellowships recognized by the EUS and SUO. Directors were surveyed on the laparoscopic case volume, degree of oncology training, and career choice of their graduates. Data were analyzed with Wilcoxon rank-sum and Student t tests. RESULTS: Our survey had an overall response rate of 60%. Fellows performed more than 100 laparoscopies during their training period in 57% of EUS and 25% of SUO fellowship programs. Similar trends are demonstrated when analyzing robotic procedures, with 73% of EUS fellows performing more than 50 procedures compared with 43% of SUO fellows. The majority (59%) of EUS programs provide oncologic training. Between 44% and 100% of graduates from EUS and SUO fellowships obtain academic positions. The majority of SUO directors (63%) believe that fellowship training in laparoscopy should be provided in fellowships governed solely by the SUO, while 41% of EUS directors believe this training should be governed solely by the EUS. CONCLUSIONS: Endourology fellowships currently provide a greater exposure to laparoscopy and robotics than SUO fellowships. The percentage of fellows seeking academic positions is similar for EUS and SUO fellowship programs and has remained stable for several years. Directors of fellowship programs that offer advanced laparoscopic training have divergent views as to which administrative body should govern its future.

Wireless teleradiology for renal colic and renal trauma.

BACKGROUND PURPOSE: Image transmission is an integral part of telemedicine, allowing evaluation of patients at remote sites. We developed a simple method of wireless transmission of digital images to a hand-held computer (PDA) and evaluated its feasibility and diagnostic accuracy in patients with acute renal colic or renal trauma. MATERIALS AND METHODS: The CT images from 11 patients with suspected renal colic and one patient with renal trauma were transmitted using a cellular telephone with a wireless modem link to a PDA (Sony Clie 615C). A diagnostic interpretation was recorded for the presence/absence of an upper-tract stone, stone location, estimated stone size, and signs of upper-tract obstruction. Radiologic staging of trauma was provided in the patient with a renal injury. Comparison was made with the final dictated report of a staff radiologist. RESULTS: Ten CT sets of patients with renal colic were used for comparison, the remaining one being excluded because of ambiguity in the final radiology report. An average of 5.9+/-1.6 images, average size 32.2+/-5.2 kb (range 21-42 kb) for each patient were sent at an average speed of 1 kb/sec. Interpretation correctly identified stone presence in 80%, hydronephrosis in 100%, and perinephric stranding in 80% and stone size within 1+/-1 mm. A stage-3 renal trauma was correctly identified and staged. CONCLUSION: Wireless teleradiology to PDA units provides image quality sufficient for diagnostic interpretation. Anticipated improvements in wireless transmission and PDA screen image resolution will enhance the speed, quality, and quantity of images transmitted. Wireless teleradiology may facilitate convenient rapid evaluation of patients at remote sites.

The evolution and progress of ureteroscopy.

Technology and refinements in urology have prospered with the bonding of engineers and surgeons. The introduction of fiberoptics and the development of the ureteroscope opened the doors to the field of ureteroscopy. Advances in rigid and flexible ureteroscopy with irrigating and working channels have expanded the capability of the urologist to diagnose and treat most abnormalities of the upper tracts in adult and pediatric populations. Instrument development has easily paralleled the growth and development of the ureteroscope and has improved success, patient safety, and comfort with the incorporation of access sheaths, nitinol materials, and Ho:YAG laser technology. Owing to their minimal morbidity and high success rate, ureteroscopic evaluation and therapeutic interventions in the upper tract represent the gold standard of management. Albert Einstein said, "There are only two ways to live your life. One is as though nothing is a miracle. The other is as though everything is a miracle." Contemporary ureteroscopy is a historical miracle that has opened a vista of endless limits in upper tract endoscopy (Fig. 4, Box 1).

Ureteroscopic treatment of renal calculi.

Although ureteroscopic treatment of renal calculi is safe and effective. it is relatively inefficient compared with ESWL and PCNL. It should be considered primary therapy for patients with lower pole stones who have adverse ESWL characteristics and patients who are not suitable candidates for PCNL. There are also numerous clinical situations, as outlined previously, where the ureteroscopic approach is favored over other treatment modalities.